Laminar Flow-Based Separations of Colloidal and Cellular Particles

ABSTRACT

A system, method and apparatus employing the laminar nature of fluid flows in microfluidic flow devices in separating, sorting or filtering colloidal and/or cellular particles from a suspension in a microfluidic flow device is disclosed. The microfluidic flow device provides for separating a particle within a suspension flow in a microfluidic flow chamber. The chamber includes a microfluidic channel comprising at least one inlet port for receiving a suspension flow under laminar conditions, a first outlet port and a second outlet port. The chamber further includes an interface for translating a particle within the channel. The first outlet port receives a first portion of the suspension exiting the said channel and the second outlet port receives the particle in a second portion of the suspension exiting the channel.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of U.S. ProvisionalPatent Application Serial No. 60/354,372 filed on Feb. 4, 2002 is hereinincorporated in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to a general class of devices thatuniquely employ laminar flows in separating, filtering or sortingcolloidal or cellular particles from a suspension within microfluidicdevices.

BACKGROUND OF THE INVENTION

[0003] Microfluidic flows are particularly useful due to their ultralaminar nature that allows for highly precise spatial control overfluids, and provides both unique transport properties and the capabilityfor parallelization and high throughput. These qualities have mademicrofluidic platforms a successful option for applications in printing,surface patterning, genetic analysis, molecular separations and sensors.Specifically, the effective separation and manipulation of colloidal andcellular suspensions on the microscale has been pursued with keeninterest due to the tremendous multidisciplinary potential associatedwith the ability to study the behavior of individual particles andcells. Devices that employ electric fields to direct flow for thepurpose of sorting and manipulating populations of cells have beenrealized and in some cases have demonstrated potential to achieveefficiencies comparable to their conventional analog, fluorescentactivated cell sorters (FACS).

SUMMARY OF THE INVENTION

[0004] The present invention relates to a system, method and apparatusemploying the laminar nature of fluid flows in microfluidic flow devicesin separating, sorting or filtering colloidal and/or cellular particlesfrom a suspension in a microfluidic flow device. In one embodiment, amicrofluidic flow device is provided for separating a particle within asuspension flow in a microfluidic flow chamber. The chamber includes amicrofluidic channel comprising an inlet port for receiving a suspensionflow under laminar conditions, a first outlet port and a second outletport. The chamber further includes an interface for translating aparticle within the channel. The first outlet port receives a firstportion of the suspension exiting the channel and the second outlet portreceives the particle in a second portion of the suspension exiting thechannel.

[0005] An alternative microfluidic flow device for separating a particlefrom a suspension flow into a second fluid flow is also provided. Themicrofluidic flow device includes a microfluidic channel comprising afirst inlet port for receiving the suspension flow, a second inlet portfor receiving the second fluid flow, a first outlet port and a secondoutlet port. The channel is adapted to receive the suspension flow andthe second fluid flow under laminar conditions. The device furtherincludes an interface for translating a particle from the suspensionflow to the second fluid flow. The first outlet port is adapted toreceive at least a portion of the suspension flow exiting the channeland the second outlet port is adapted to receive the particle in atleast a portion of the second fluid flow exiting channel.

[0006] A method of separating a particle within a suspension is alsoprovided in which a suspension flow is received in a microfluidicchannel under laminar conditions. A particle in the suspension istranslated within the suspension flow. A first portion of the suspensionflow exits through a first outlet port, and the particle exits in asecond portion of the suspension flow through a second outlet port.

[0007] Another method of separating a particle from a suspension flow isprovided in which a suspension flow and a second fluid flow are receivedin a microfluidic channel. The suspension and the second fluid flowunder laminar conditions in the channel. A particle is separated fromthe suspension flow into the second fluid flow. At least a portion ofthe suspension flow exits through a first outlet port, and the particleexits in at least a portion of the second fluid flow through a secondoutlet port.

[0008] A cartridge is also provided for use in system to separate aparticle from a suspension flow. The cartridge comprises a microfluidicchannel including an inlet port for receiving a suspension flow underlaminar conditions, a first outlet port and a second outlet port. Thecartridge further comprises an interconnect for connecting the cartridgeto the system. The microfluidic channel is adapted to receive thesuspension flow and provide an environment for translating the particlewithin the suspension flow. The first outlet port is adapted to receivea first portion of the suspension flow, and the second outlet port isadapted to receive the particle in a second portion of the suspensionflow.

[0009] An alternative cartridge is further provided for use in system toseparate a particle from a suspension flow into a second fluid flow. Thecartridge comprises a microfluidic channel including a first inlet portfor receiving the suspension flow, a second inlet port for receiving thesecond fluid flow, a first outlet port and a second outlet port. Thechannel is further adapted to receive the suspension flow and the secondfluid flow in the channel under laminar conditions. The cartridgefurther comprises an interconnect for connecting the cartridge to thesystem. The microfluidic channel is adapted to provide an environmentfor translating the particle from the suspension flow to the secondfluid flow. The first outlet port is adapted to receive at least aportion of the suspension flow, and the second outlet port is adapted toreceive the particle in at least a portion of the second fluid flow.

[0010] A system for separating a particle from a solution in amicrofluidic flow device is also provided. The system includes adetector, an information processor and an actuator. The detectormonitors a microfluidic channel of the microfluidic flow device andprovides an output to the information processor. The informationprocessor processes the output to determine if the particle is present.If the particle is present, the information processor triggers theactuator to translate the particle within the channel.

[0011] A microfluidic chemical dispenser for dispensing a fluid flowinto a plurality of receptacles is further provided. The dispensercomprises a first inlet port, a second inlet port, a third inlet port, acentral channel, a plurality of outlet ports, and a modulator. Thechannel is adapted to receive, under laminar conditions, a first fluidflow through the first input port, a second fluid flow through thesecond input port and a third fluid flow through the third input port.The second input port is positioned at a first angle to the first inputport, and the third input port is positioned at a second angle to thefirst input port. The modulator modulates the flow rates of the secondand third fluid flows to dispense the first fluid flow into a pluralityof outlet ports.

[0012] The foregoing and other features, utilities and advantages of theinvention will be apparent from the following more particulardescription of a preferred embodiment of the invention as illustrated inthe accompanying drawings.

Brief Description of the Drawings

[0013]FIG. 1 depicts a flow diagram of an actuated process of separatinga colloidal or cellular particle from a suspension in a microfluidicflow device;

[0014]FIG. 2 depicts a block diagram of an exemplary system forseparating a colloidal or cellular particle from a suspension in amicrofluidic flow device;

[0015]FIG. 2a depicts a block diagram of a microfluidic flow networkthat may be used in conjunction with the system depicted in FIGS. 2, 3and 4;

[0016]FIG. 3 depicts a block diagram of an alternative system forseparating a colloidal or cellular particle from a suspension in amicrofluidic flow device;

[0017]FIG. 4 depicts a block diagram of another alternative system forseparating a colloidal or cellular particle from a suspension in amicrofluidic flow device, wherein the system controls a valve actuatorto separate the particle from the suspension;

[0018]FIG. 5 depicts a fluid flow path in one example of a microfluidicflow chamber;

[0019]FIG. 5a depicts a particle entering the microfluidic flow chamberdepicted in FIG. 5 via an inlet port;

[0020]FIG. 5b depicts the particle depicted in FIG. 5a being movedwithin a central channel of the microfluidic flow chamber depicted inFIG. 5;

[0021]FIG. 5c depicts the particle depicted in FIG. 5a exiting thecentral channel of the microfluidic flow chamber depicted in FIG. 5 viaan outlet port;

[0022]FIG. 6 depicts side-by-side laminar fluid flows in the centralchannel of the microfluidic flow chamber depicted in FIG. 5;

[0023]FIG. 6a depicts a particle entering the central channel via aninlet port of the microfluidic flow chamber in the first fluid flowdepicted in FIG. 6;

[0024]FIG. 6b depicts the particle depicted in FIG. 6a being movedwithin the central channel of the microfluidic flow chamber from thefirst flow to the second flow;

[0025]FIG. 6c depicts the particle depicted in FIG. 6a exiting thecentral channel of the microfluidic flow chamber in the second flow viaan outlet port;

[0026]FIG. 7 depicts an alternative example of a microfluidic flowchamber;

[0027]FIG. 7a depicts side flows pinching a central flow of a suspensionat the entrance to a central channel of the microfluidic flow chamberdepicted in FIG. 7 to orient the flow of suspension in the centerportion of the channel;

[0028]FIG. 7b depicts side flows pinching a central flow of a suspensionat the entrance to a central channel of the microfluidic flow chamberdepicted in FIG. 7 to orient the flow of suspension in the bottomportion of the channel;

[0029]FIG. 7c depicts side flows pinching a central flow of a suspensionat the entrance to a central channel of the microfluidic flow chamberdepicted in FIG. 7 to orient the flow of suspension in the top portionof the channel;

[0030]FIG. 8 depicts another example of a microfluidic flow chamberincluding a plurality of outlet ports for sorting colloidal and/orcellular particles in a suspension;

[0031]FIG. 9 depicts a microfluidic flow chamber including a mechanicalactuator for separating a colloidal and/or cellular particle in asuspension, wherein the mechanical actuator comprises a valve;

[0032]FIG. 9a depicts an alternative example of a microfluidic flowchamber including a mechanical actuator for separating a colloidaland/or cellular particle in a suspension, wherein the mechanicalactuator comprises a valve;

[0033]FIG. 9b depicts the particle being separated from the suspensionvia the valve of the microfluidic chamber depicted in FIG. 9a beingclosed to divert the particle into an alternative outlet port;

[0034]FIG. 9c depicts the particle exiting the alternative outlet portof the microfluidic chamber depicted in FIG. 9a and the valve retractingto its open position;

[0035]FIG. 9d depicts another alternative example of a microfluidic flowchamber including a chemical actuator for separating a colloidal and/orcellular particle in a suspension, wherein the chemical actuatorcomprises a chemically actuated valve;

[0036]FIG. 9e depicts the particle being separated from the suspensionvia the valve of the microfluidic chamber depicted in FIG. 9d beingswollen closed to divert the particle into an alternative outlet port;

[0037]FIG. 9f depicts the particle exiting the alternative outlet portof the microfluidic chamber depicted in FIG. 9d and the valve shrinkingto its open position;

[0038]FIG. 10 depicts a series of suspensions being introduced into amicrofluidic flow chamber in series separated by buffers;

[0039]FIG. 11 depicts an alternative non-actuated microfluidic flowdevice for separating colloidal and/or cellular particles from asuspension;

[0040]FIG. 12 depicts another alternative non-actuated microfluidic flowdevice for separating colloidal and/or cellular particles from asuspension;

[0041]FIG. 13 depicts an exemplary non-actuated microfluidic flow devicefor sorting colloidal and/or cellular particles from a suspension bysize;

[0042]FIG. 14 depicts an alternative non-actuated microfluidic flowdevice for separating motile cellular particles from a suspension;

[0043]FIG. 15 depicts an exemplary non-actuated microfluidic flow devicefor separating colloidal and/or cellular particles from a suspension;and

[0044]FIG. 16 depicts a cartridge including a microfluidic flow chamber.

Detailed Description

[0045] The processes and devices described herein relate to actuated ornon-actuated separation of various colloidal and/or cellular particlesfrom a suspension flowing under laminar conditions in a microfluidicflow device. The colloidal and cellular particles may include, forexample, polymeric, inorganic or other abiotic colloidal particles,individual polymers, proteins, fragments of DNA or RNA, entire sectionsor genomes of DNA, cells including single-celled organisms, formedbodies such as they would appear in blood, viruses and the like. Amicrofluidic flow device, as used for the purposes of the presentinvention, refers to a microscale device that handles volumes of liquidon the order of nanoliters or picoliters.

[0046] Under “laminar” flow conditions, a fluid flows through a channelwithout turbulence. The quantification of laminar or nonturbulentbehavior is typically done through calculation of the Reynolds number,Re=ρνD/η, where ρ is the fluid density, η is the fluid viscosity, ν isthe fluid velocity, and D is some characteristic channel dimension(typically the channel width). If the Reynolds number is small (<1000)for typical channel geometries, then flow is laminar, reversible, andnon-turbulent. For this reason, the diameter of the channel can bedesigned to account for the intended fluid properties and fluidvelocity, or, equivalently, the fluid velocity can be determined by thefluid properties and the channel diameter.

[0047]FIG. 1 shows a flow diagram of a process for an actuatedseparation of colloidal and/or cellular particles from a suspensionflowing through a microfluidic flow device under laminar conditions. Inthe receive input block 10, an input is received from a sensormonitoring a target region for a particle of interest. The target regionmay be monitored to detect any known attribute (or absence thereof) thatcan be used to distinguish a particle from the remaining suspension. Animaging device such as a charge-coupled device (CCD) camera, forexample, may be utilized to capture a stream of images that may be usedto identify a particle by its particular morphological attributes ormotility. Alternatively, signatures, fingerprints or indices such as afluorescent signature, light scattering signature, optical fingerprint,X-ray diffraction signature or index of refraction, and the like, or anycombination of these, may be used to distinguish the particle from theremaining suspension. Surface charges of particles may also be used todistinguish the particle by observing the reaction of the particle to anapplied electric or magnetic field.

[0048] Further, the suspension or the individual particles may bepretreated, as known in the art, to enhance the recognition of theparticles. The suspension may further be pretreated with an antibodythat will bind specifically to a particular type of particle may be usedto enable or enhance the recognition of the particle. A suspension ofcells, for example, may be pretreated with antibody-decorated magneticparticles and passed through a magnetic field to distinguish theparticles from the remaining suspension. Similarly, other recognitionmethodologies known in the art may be used to distinguish the particleof interest from the remaining suspension.

[0049] Information processing block 20 performs any processing stepsnecessary to distinguish the particle from the remaining suspension suchas comparing received images or signals from the receive input block 10to threshold values, e.g., size and shape. The information processingblock 20 may include any required processing steps as known in the artto distinguish the particle of interest from the remaining suspension.The processing steps may vary depending upon the type of input received.The processing step, for example, may include simple recognition of adigital input value or may include complicated processing steps todetect whether a given input corresponds to the presence of a particleof interest.

[0050] After a particle is identified, the particle may be separatedfrom the suspension by the actuation of separation block 30. Theactuation may include, for example, steering an optical trap such as viaa piezoelectric mirror, an acoustic optic deflector, a diffractiongrating, a holographically-generated trap, a static line trap, a dynamicline trap, an optical gradient, a microlens array, a waveguidingstructure or other known optical steering mechanism. The actuation mayalternatively include generating an electric field or a magnetic field.The actuation may also include a mechanical or chemical actuator. Amechanical actuator, for example, may include a pump, valve, gate,applied pressure and the like. A chemical actuator, for example, mayinclude a hydrogel or similarly behaving material that reacts to aproperty sensed in the suspension that may indicate the presence orabsence of a particle of interest.

[0051] Each of the functions shown in blocks 10, 20 and 30 of FIG. 1,however, need not be performed by distinct hardware components. Asensor, for example, may receive an input and perform the informationprocessing on that input to determine if a particle of interest has beendetected. An actuator may even perform each of the functions by directlyreacting to a property being monitored (e.g., a pH responsive hydrogelmay swell in response to a sensed pH level).

[0052]FIG. 2 shows one exemplary system 40 for separating a particle ofinterest from a suspension in a microfluidic flow device 44 utilizing anactuated separation technique. The system includes an detector system50, an information processing system 60 and an actuator system 70. Thedetector system 50 includes an imaging system, such as a camera 52, thatmay be used to image a field of view through a filter 54 and amicroscope 56. The detector system 50, for example, may utilize a CCDcamera to capture a stream of images of the microfluidic flow devicethrough a microscope lens. In one particular embodiment, the camera 52captures images at a rate of 30 images per second through a 100Xobjective. The images are recorded by a recording device, such as VCR58, and/or passed directly to an information processor, such as acomputer 62. Optionally, the identification of the particles may beaided by utilizing the laser 74 or another light source, such as asecondary laser, multiple other lasers, a broad spectrum lamp and thelike, to irradiate the suspension to illuminate the particles ofinterest.

[0053] The information processor may include the computer 62, acontroller or other processor known in the art. The informationprocessor receives and processes the image data and distinguishes theparticle of interest from the remaining suspension as described above.Once the particle is recognized, the information processor may triggerthe actuator system 70 to separate the particle from the suspension.

[0054] The actuator system 70 may include a targeting device 72 totarget a laser beam from a laser 74 on the microfluidic flow device 44.The targeting device, for example, may include a piezo drive 76 tocontrol a piezo mirror 78 to direct the beam of a laser 74. The laser74, when focused on the particle, traps the particle. The optical trapmay then be used to translate the particle between streams in thechannel of the microfluidic flow device 44.

[0055] Utilizing an optical trap as the means of actuation provides thecapability for highly precise and immediately customizable individualseparations. Other applied fields, however, may also be utilized totranslate particles from the primary stream to the secondary stream.Both electric and magnetic fields may be employed with appropriatesuspensions to isolate individual or multiple particles. All colloidalparticles and living cells carry with them a surface charge, which, inthe presence of an electrical field results in electrophoresis. Theelectrophoretic force, or the migration of surface ions with an electricfield, is sufficient to translate cells or particles from one stream toanother. Similarly, if a particle or cell possesses a magnetic moment,it may be selectively translated in a magnetic field. Each of thesefields could be applied continuously to fractionate particles or cellsbased on electrical or magnetic properties, or could be pulsed orapplied discriminatively for custom separations.

[0056] As described above, the suspension or the individual particlesmay be pretreated, as known in the art. The pretreatment, for example,may enhance the response of the particle to an optical trap or electricor magnetic field. The suspension may further be pretreated with items,such as antibodies that will bind specifically to a particular type ofparticle may be used to enable or enhance the movement of the particlevia an optical trap or electric or magnetic field. A suspension ofcells, for example, may be pretreated with antibody-decorated magneticparticles and, thus, be easily moved by means of a magnetic field.

[0057]FIG. 2a shows further detail of a microfluidic flow device 44 thatmay be used in connection with a system 40, 80 and 110 such as shown inFIGS. 2, 3 and 4, respectively. The microfluidic flow device 44 includesa flow generator 45, which provides a pressure differential to inducefluid flows through the microfluidic flow device 44. The pressuredifferential, for example, may be induced by any method known in the artsuch as, but not limited to, capillary forces; gravity feed;electro-osmosis systems; syringes; pumps such as syringe pumps (e.g., akdScientific, model 200 syringe pump), peristaltic pumps and micropumps;valves such as three-way valves, two-way valves, ball valves andmicrovalves; suction; vacuums and the like. Further, although FIG. 2ashows the flow generator located upstream of a microfluidic flow chamber47, the flow generator may also be placed midstream in the microfluidicflow chamber 47 or downstream of the microfluidic flow chamber 47.Further, the microfluidic flow chamber 47 preferably provides at leastone output 49 with the collected particles separated from a suspensionwithin the chamber. This output 49 may provide the collected particlesas an end process or may provide the particles to a downstream networkfor further processing.

[0058]FIG. 3 shows an alternative system for separating a particle ofinterest from a suspension in a microfluidic flow device. The imagingsystem 90 and its operation is the same as shown in FIG. 2 except thatthe imaging system 90 further includes a field generator 92. The fieldgenerator 92 induces an electric or magnetic field in the microfluidicflow device 44. As the suspension flows through the device 44, themovement of the particles of interest, whether induced by electric ormagnetic properties of the particles themselves or by propertiesassociated with a pretreatment of the particles, is captured by theimaging system 90 and identified by the information processor 100.

[0059]FIG. 4 shows another system 110 for separating a particle ofinterest from a suspension in a microfluidic flow device 114. In thissystem, the actuator system includes a valve controller 112 thatcontrols the operation of a valve within the microfluidic flow device114. The valve, for example, may be opened to divert the flow of thesuspension within the microfluidic flow device for a predetermined timeafter the recognition of the particle of interest. In this manner, thesystem separates the particle in a small portion of the suspension bydiverting the suspension carrying the particle into an alternativeoutlet port. An example of such a valve is described below with respectto FIGS. 9a- 9 c.

[0060] A particular microfluidic flow channel can be modeled todetermine the flow path of a fluid flowing in a laminar manner throughthe channel. This is well known in the art and involves solving theLangevin equations, the Navier-Stokes equations or other equations ofmotion, which can be done manually or electronically. Commercialsoftware tools are also available for modeling the laminar flow path ofa fluid through any microfluidic flow channel. For example, CFDASE, afinite element modeling for computational fluid dynamics moduleavailable from Open Channel Foundation Publishing Software from Academic& Research Institutions of Chicago, Ill., and FIDAP, a flow-modelingtool available from Fluent, Inc. of Lebanon, N.H., can be used to modelthe laminar flow of a fluid through a particular microfluidic channel.

[0061]FIG. 5 shows an embodiment of a microfluidic flow chamber 120 inwhich a particle of interest may be separated from a suspension. Themicrofluidic flow chamber includes a single inlet port 122, two outletports 124 and 126 and a central channel 128. FIG. 5 further shows arrowsdepicting a modeled laminar flow of a particular fluid through themicrofluidic flow chamber 120. FIG. 5a- 5 c show a process forseparating a particle 130 from a suspension flow in the microfluidicflow chamber 120 of FIG. 5. FIG. 5a shows the particle entering themicrofluidic flow chamber 120 via the inlet port 122 at which point itis identified as described above. The information processor initiates anactuator to direct the particle 130 into a desired portion of the flowstream 132 of the suspension in FIG. 5b. Thus, the particle 130 isdirected to a portion of the flow in which it will exit the centralchamber 128 through the second outlet port 126, as shown in FIG. 5c.

[0062]FIGS. 6 and 6a- 6 c show an alternative embodiment of amicrofluidic flow chamber 140, which includes two inlet ports 142 and144, a central channel 146 and two outlet ports 148 and 150. As FIG. 6shows, a first fluid 152, indicated by dye, enters the central channel146 via the first inlet port 142 and a second fluid 154 enters thecentral channel 146 via the second inlet port 144. As described above,when the first fluid 152 and the second fluid 154 flow through themicrofluidic flow chamber in a laminar manner, the fluids maintainseparate streams and undergo minimal convective mixing. Rather, themixing present is primarily due to molecular-scale diffusion, which forcolloidal-sized particles is referred to as Brownian movement, as shownnear the outlet port of the central channel. The system can be designedto minimize the diffusion that occurs within the central channel 146 bycontrolling the central channel 146 dimensions and the velocity of thefluid flowing through the channel 146. In general, the diffusiondistance x, can be expressed as x ≈{square root}{square root over ()}D·t, wherein D is the diffusivity and t is the time. To a first order,the diffusivity is inversely proportional to the size of the particle.Therefore, to a first order, the channel residence time required toachieve complete mixing, t≈x²D⁻¹ scales linearly with the particlediameter. Thus, by designing the microfluidic flow chamber dimensionsfor a particular flow rate of a fluid, a laminar two-phase flow may beused as an effective barrier against particle cross-transport. In theexample shown in FIG. 6, each of the inlet streams has a width of about30 μm and the central channel has a length from the inlet ports to theoutlet ports of about 3000 μm, the reduction of which willcorrespondingly reduce the diffusion within the channel 146 for aconstant flow rate. Both of the fluids streams 152 and 154 shown arewater. The first stream 152 includes a molecular dye (Methylene Blue),which has a diffusion coefficient on the order of about 1×10⁻⁵ cm²/secin water.

[0063] Further, as shown by the dashed line in FIG. 6a, a portion of thesecond fluid stream 154 can exit the central channel 146 via the firstoutlet port 148 while the remainder of the second fluid 154 exits viathe second outlet port 150. If the first fluid 152 is a suspensionincluding suspended particles and the second fluid 154 is a cleansolvent, for example, the portion of the solvent that exits the firstoutlet port 148 along with the suspension 152 acts as an additionalbarrier to cross-contamination of the streams through diffusion. Thus,particles that diffuse into this portion of the solvent stream may stillexit the central chamber 146 via the first outlet port 148, as shown inFIG. 6.

[0064] The steady state flow-based particle barrier can be penetrated,however, by providing an actuator to move a particle 156 across thebarrier. A selective activation of an electric, magnetic or opticalfield, or any combination of these fields, for example, may be used tomove the particle 156 from one stream to another stream. Alternatively,a mechanical actuator, such as a valve, pump, gate or applied pressuremay be employed to move the particle from one stream to another stream.Although described here for parallel flows, the flows traveling inarbitrary orientations, including opposite directions, are possible.

[0065]FIGS. 6a- 6 c show a particle 156 being separated from the firstinlet stream 152 into the second inlet stream 154 in the embodimentshown in FIG. 6. In FIG. 6a, a suspension enters the central channel 146from the first inlet port 142, and a second fluid 154, such as asolvent, enters the central channel 146 from the second inlet channel144. The suspension 152 and the second fluid 154 flow in a laminarmanner through the central channel 146. The suspension stream 152 and aportion of the second fluid stream 154 exit the central channel 146 viathe first outlet port 148. The remaining portion of the second fluidstream 154 functions as a collection stream and exits the centralchannel 146 via the second outlet port 150. A particle 156 suspended inthe suspension stream 152 is shown entering the central channel 146 fromthe first inlet port 142, where it is identified as described above. InFIG. 6b, the particle 156 is shown being separated from the suspensionstream 152 into the second fluid stream 154. The particle 156 may beseparated from the suspension 152 via an electrical, magnetic,mechanical or chemical actuator such as described above. In FIG. 6c, theparticle 156 is shown exiting the central channel 146 via the secondoutlet port 150 in the second fluid stream 154 for collection.

[0066]FIG. 7 shows another embodiment of a microfluidic flow chamber 160in which a particle of interest may be separated from a suspension. Themicrofluidic flow chamber 160 includes three inlet ports 162, 164 and166, two outlet ports 168 and 170 and a central channel 172. In thisexample, a suspension including suspended particles enters from thefirst inlet port 162. Other fluid streams, such as a pair of solvent orbuffer fluid streams enter the central channel 172 from either side ofthe first inlet port 162. As shown in FIGS. 7a- 7 c, the relative flowrates of each inlet port may be modulated to vary the resulting incomingstream 174 into the central channel 172. In FIG. 7a, for example, therelative flow rates of the streams in the second inlet port 164 and thethird inlet port 166 are relatively equal and pinch the flow from thefirst inlet port 162 at a neck and form a narrow stream of the firstfluid approximately down the center of the central channel 172. Byvarying the flow rates of the second and third inlet streams 164 and166, the width of the first fluid stream 174, i.e., the suspension, canbe narrowed down to the width of a single particle. Thus, the inletsample suspension 174 may be “prefocused” into a narrow, or even singlefile, particle stream surrounded on either side by a potentialcollection stream. This allows for a decrease in the lateral distance,i.e., distance perpendicular to the flow direction, a particle must bemoved away from the suspension stream to be captured in the collectionstream and, thus, an increase in sorting efficiency.

[0067]FIG. 7b shows the embodiment of FIG. 7, wherein the flow rate ofthe third inlet port 166 is less than the flow rate of the second inletport 164 and prefocuses the inlet particle stream in the lower half ofthe central chamber 172. Conversely, FIG. 7b shows the embodiment ofFIG. 7, wherein the flow rate of the third inlet port 166 is greaterthan the flow rate of the second inlet port 164 and prefocuses the inletparticle stream in the upper half of the central chamber 172. Therelative flow rates of the three inlets can thus be modulated to controlthe particle stream within the central channel.

[0068]FIG. 8 shows yet another embodiment of a microfluidic flow chamber180 in which a particle of interest may be separated from a suspension.As in FIG. 7, the microfluidic flow chamber 180 includes three inletports 182, 184 and 186 and a central channel 188. The chamber 180 ofFIG. 8, however, includes six outlet ports 188, 190, 192, 194, 196 and198. The number of outlet ports shown in FIG. 8 is merely exemplary andmay include any number of outlet ports greater than or equal to two. Inthis example, the plurality of outlet ports may be used to sort aplurality of particles into various outlet ports. Different types ofparticles, for example, may be sorted into different outlet ports.Alternatively, the plurality of outlet ports may be used to individuallysort the same type of particles into different outlet ports. In yetanother embodiment, the side flows may be modulated as described aboveto dispense particles, chemicals and/or fluids (e.g., reagents) intomultiple outlet ports for use in various downstream applications ornetworks.

[0069] Alternatively, the incoming streams may be prefocused prior toentry into the microfluidic flow chamber, or the side inlet ports may bearranged to enter the central channel downstream of the first inletport.

[0070]FIG. 9 shows an embodiment of a microfluidic flow chamber 200 inwhich a particle of interest may be separated from a suspension via amechanical actuator. As shown in FIG. 9, the central channel 202includes a side channel 204 through which incoming fluid flow iscontrolled by a valve 206. After a particle is detected, the valve maybe opened to vary the fluid flow within the central channel 202 anddivert the suspension along with the particle away from the first outletport 208 into the second outlet port 210. Alternatively, the valve 206may be closed or the flow through the valve may be merely adjusted todivert the particle into the desired outlet port. Similarly, the valve206 may be positioned on the opposite side of the central chamber 202and may obtain a similar result by providing or modulating the flow inthe opposite direction.

[0071]FIGS. 9a- 9 c show yet another embodiment of a microfluidic flowchamber 220 in which a particle of interest may be separated from asuspension via a mechanical actuator. As shown in FIG. 9a, the particle222 enters the central channel 224 in the suspension via the first inletport 226. In FIG. 9b, the valve 228 activates after the particle isidentified as described above and redirects the particle 222 into thesecond outlet port 230. Then, in FIG. 9c, after the particle 222 hasexited the central channel 224, the valve 228 retracts and the fluidstream flows return to their steady state condition.

[0072]FIGS. 9d- 9 f show an exemplary microfluidic flow chamber 240 inwhich a particle of interest may be separated from a suspension via achemical actuator. As shown in FIGS. 9d 9 f, the microfluidic flowchamber 240 includes a chemical actuator material 242, such as ahydrogel, that swells or shrinks in reaction to an attribute associatedwith a particular particle of interest (e.g., pH). Hydrogels, such asthese are known in the art. Beebe, David J. et al, “Functional HydrogelStructures for Autonomous Flow Control Inside Microfluidic Channels,Nature, vol. 404, pp. 588-90, (Apr. 6, 2000), for example, discloseshydrogel actuators that may be used in the present embodiment.

[0073]FIGS. 9d- 9 f show a chemically actuated valve 244 including thechemical actuator material 242. In FIG. 9d, for example, the chemicalactuator is in its normal condition in which the valve 244 is open andthe suspension flows through the first outlet port 246. FIG. 9e showsthe chemical actuator in its active state in which the chemical actuatormaterial 242 is swollen in response to a detected attribute, effectivelyshutting off the first outlet port 246 and the suspension flows throughthe second outlet port 252 and allowing the particle 250 of interest tobe collected. Although FIG. 9e shows the chemically actuated valve 244completely closing off the first outlet port, the swelling of thechemically actuated material 242 may also merely create a barrier toparticular-sized particles while allowing the remainder of thesuspension to pass into the first outlet port 246. Where the individualvalve members are angled toward the second outlet port 252, the blockedparticles 250 may be conveyed to the second outlet port 252 forcollection. FIG. 9f further shows the chemically actuated valve 244returned to its open condition after the detected particle 250 haspassed into the second outlet port 252.

[0074] Alternatively microfluidic flow devices may employ laminar flowsand specific microgeometries for non-actuated separation of colloidaland/or cellular particles in fluid suspensions. The geometry of thesedevices has been designed to act similarly to a filter without the useof membranes or sieves which are highly susceptible to clogging andfouling. Such devices will also be capable of replacing thecentrifugation step common to many biological processes upon a chipsurface. With a microscale alternative to centrifugation available, ahost of multi-step biological processes such as bead-based assays andcell counting using dying techniques will be able to be performed withinmicrofluidic devices.

[0075] As demonstrated in FIGS. 10 12, specific channel geometries maybe created to take advantage of the laminar nature of fluids flowing inmicrochannels. In each of these designs, the particle suspension entersthe central channel 260 through a first inlet port 262. A second fluidstream, such as a solvent stream, enters the channel 260 through asecond inlet port 264, which meets the first inlet port 262 at anyangle. Because of the laminar nature of microfluidic flows, thesestreams will generally not mix convectively. The central channel 260further includes microscale obstacles 265. Molecular debris small enoughto fit through the openings formed by the microscale obstacles 265 willbe carried down the first outlet port 266. Due to the presence ofmicroscale obstacles, however, any particles larger than the separationof the obstacles will be shuffled toward the second outlet port 268 andexit the central channel 260 with a portion of the second fluid stream.The designs shown here do not depend upon relative channel size, insteadthe presence of the microscale obstacles at or near the confluence ofthe two (or more) inlet streams alter the direction of flow for anyparticulate matter in the suspension inlet stream(s).

[0076]FIG. 13 further shows a configuration for sorting particles in thesuspension by size and produces a size fractionation effect by designingthe size of the gaps 274 between the guides 276 to increase away fromthe first inlet port 262, by which the suspension is introduced into thecentral channel 270. By gradually increasing the widths of the gaps 274moving away from the first inlet port 262, particles of increasing sizeflow into the guides 276 and may be collected individually.

[0077]FIG. 14 shows yet another embodiment of a non-actuated separationof motile particles within a suspension between laminar flows. In thisembodiment, motile particles 280 entering in the suspension flow 282move within the suspension flow and can pass from the suspension flow282 into the second fluid stream 284 without the need of an actuator toseparate the particles 280 from the suspension flow 282. In this manner,the motile particles 280 may enter the second fluid stream 284 and exitthe central channel 286 through the second outlet port 290 instead ofthe first inlet port 288. For example, in a suspension 282 containingsperm, the active sperm may move on their own into the second fluidstream 284 for collection, while inactive sperm are carried out of thecentral channel 286 with the suspension 282 via the first outlet port288.

[0078] Non-actuated separation of colloidal and/or cellular particlesfrom a suspension in a microfluidic flow device presents a very simpleapproach to microfluidic separations or enrichments of colloidal and/orcellular particles because it relies upon the condition native to fluidsflowing on the microscale, regardless of flow rate or channelmorphology: laminar flows. Furthermore, the selection of materials forthe construction of these devices is irrelevant, thus they may beincorporated into microfluidic devices constructed on any substrate.

[0079]FIG. 15 shows another example of a microfluidic flow chamber inwhich a series of discrete sample suspensions 300 are combined into asingle laminar flow. In this example, a plurality of discrete samples300 form the single sample flow. The sample flow further preferablyincludes buffers 302 between each discrete sample 300 to preventcross-contamination between samples 300. In this manner, a singlemicrofluidic flow chamber 304 can separate particles from a series ofsamples to increase throughput. The series of discrete samplesuspensions may, for example, be created using a microfluidic dispenseras shown and described above with reference to FIG. 8 in whichindividual samples are directed into a plurality of outlet ports andcombined downstream into a series of discrete sample streams.

[0080]FIG. 16 shows a cartridge 310 that may be plugged into, orotherwise connected to, a system for separating one or more colloidal orcellular particles from a suspension. The cartridge 310 may be reusableor disposable. The cartridge may include a sample reservoir 312, orother inlet mechanism, for receiving a fluid suspension. The samplereservoir 312 is connected to a central channel 314 via a first inletport 316. The cartridge further includes a waste receptacle 318, orother outlet mechanism, connected to the central channel 314 via a firstoutlet port 320 for receiving the suspension after it has passed throughthe central channel 314 for the removal of one or more particles ofinterest. A collection receptacle 322 is also connected to the centralchannel 314 via a second outlet port 324 for receiving the particlescollected from the suspension. The collection receptacle 322 may includea reservoir or other means for holding the collected particles or mayinclude a channel or other means for providing the collected particlesto downstream networks for further processing.

[0081] The cartridge 310 may also include a second inlet reservoir 326for receiving a second fluid, may receive the second fluid from anexternal source in the system, or may not utilize a second fluid at all,such as described with reference to FIG. 5. If used, the second fluidmay include a fluid such as a buffer or a solvent (e.g., water, a salinesuspension and the like) or a reagent (e.g., antibody tagged particles,fluorescent tags, lysing agents, anticoagulants and the like), or anycombination thereof. Indeed, the fluid requirements may besystem-specific and may be matched to the intended application and modeof use. The second inlet reservoir 326 or receptacle for receiving asecond fluid, if used, may be connected to the central channel 314 via asecond inlet port 328.

[0082] The reservoirs or receptacles may include any interface fortransferring a fluid known in the art. For example, the reservoir may beadapted to receive fluids from a syringe, either with or without aneedle, from a tube, from a pump, directly from a human or animal, suchas through a finger stick, or from any specially designed or standardfluid transfer coupling.

[0083] The microfluidic flow chambers described herein may bemanufactured by a variety of common microelectronics processingtechniques. A pattern of a shadow mask may be transferred to a positiveor negative photoresist film spun upon a silicon wafer, a glass slide,or some other substrate, for example. This pattern may be sealed andused directly as the microfluidic network, replicated in anothermaterial, or further processed. The substrate may be further processedthrough subsequent wet etching, dry etching, molecular epitaxy, physicaldeposition of materials, chemical deposition of materials, and the like,or any combination of these or similar techniques. The final network maybe used directly or reproduced through the use of a replicationtechnique designed to produce a replica upon the master, such as by thepouring and curing, imprinting in or deposition of elastomers, polymersand the like. A pump or other means for introducing and controllingfluid flow within the fluidic network as well as a means for connectingthe pump or pressure differential means may also be provided. Thenetwork can further be sealed, such as with a cover slip, glass slide,silicon wafer, polymer films or a similar substrate.

[0084] In one specific, nonlimiting example, a pattern on a shadow maskwas exposed to ultraviolet light and transferred to a negativephotoresist film spun upon a silicon wafer to a depth of approximately 5μm. A two-part mixture of poly(dimethyl siloxane) (PDMS), which iscommercially available from Dow Corning under the trade name of Sylgard184, was poured and cured upon the silicon master to produce a flexible,biocompatible optically transparent replica. In addition to the PDMSchannel network a flow apparatus comprising a syringe pump such as akdScientific, model 200 syringe pump and a polymethyl methalacrylate(PMMA) flow introduction base. The PDMS channel network was placed uponthe PMMA base, and holes were punched through the PDMS to provide accessfor the microchannels to the ports in the base. The network was furthersealed with a cover slip. Because the PDMS forms a tight seal with bothPMMA and glass, no additional bonding or clamping was required. Thesyringe pump was further fitted with 3 cm³ plastic syringes (such asavailable from Becton-Dickson) joined to the base.

[0085] One embodiment of an optical trap and digital microscopy that maybe used with the microfluidic flow devices described herein mayincorporate a piezoelectric mirror (such as available from PhysikInstrumente, model S-315) to simultaneously trap several particles byrapidly scanning a single laser beam (such as available from SpectraPhysics, 532 nm, typically operated at 200 mW) among a number ofpositions to create a time-averaged extended trapping pattern. ANeofluar, 100X, oil immersion high numerical aperture objective(N.A.=1.30) can be used to focus the beam and create the optical trap.CCD images can be captured by a data acquisition board and processed byLabView (National Instruments) routines that may be customized todistinguish various visual particle or cell features for specificapplications. Optical traps and digital microscopy are described infurther detail, for example, in Mio, C.; Gong, T.; Terry, A.; Marr, D.W. M., Design of a Scanning Laser Optical Trap for MultiparticleManipulation, Rev. Sci. Instrum. 2000, 71, 2196-2200.

[0086] While the invention has been particularly shown and describedwith reference to particular embodiment(s) thereof, it will beunderstood by those skilled in the art that various other changes in theform and details may be made without departing from the spirit and scopeof the invention. One skilled in the art of microfluidic flows, forexample, would recognize that downstream or upstream analogues ofmechanisms described herein may be substituted for the particularexemplary structures disclosed herein.

1. A microfluidic flow device for separating a particle within asuspension flow, the microfluidic flow device comprising: a microfluidicchannel comprising an inlet port for receiving the suspension flow underlaminar conditions, a first outlet port and a second outlet port; and aninterface for translating the particle within said channel, wherein saidfirst outlet port is adapted to receive a first portion of thesuspension exiting said channel and said second outlet port is adaptedto receive the particle in a second portion of the suspension exitingthe channel.
 2. The microfluidic flow device of claim 1, wherein saidinterface comprises an optically transparent portion of said channel. 3.The microfluidic flow device of claim 1, wherein said interfacecomprises two or more electrodes to provide an electric field in thecentral channel.
 4. The microfluidic flow device of claim 3, whereinsaid interface further comprises an electrical interconnect forreceiving electrical energy from the system and providing the electricalenergy to said two or more electrodes.
 5. The microfluidic flow deviceof claim 1, wherein said interface further comprises a magnet forproviding a magnetic field extending into said channel.
 6. Themicrofluidic flow device of claim 1, wherein said channel is adaptedsuch that an electric field may extend into said channel for translatingthe particle within the suspension flow.
 7. The microfluidic flow deviceof claim 6, wherein said field comprises at least one or more of anoptical trap, an electrical field and a magnetic field.
 8. Themicrofluidic flow device of claim 1, where in said interface comprises achannel geometry for sorting the particle within the channel.
 9. Themicrofluidic flow device of claim 1, wherein said laminar conditionscomprise a Reynolds number of less than about
 1000. 10. The microfluidicflow device of claim 1, wherein said channel comprises a cartridge. 11.The microfluidic flow device of claim 1, wherein said channel comprisesa disposable cartridge.
 12. The microfluidic flow device of claim 1further comprising a pressure differential generator for providing fluidflow in said channel.
 13. The microfluidic flow device of claim 12,wherein said pressure differential generator comprises one or more ofthe group comprising: a pump, a capillary force generator, a gravityfeed generator, an electro-osmosis system, a syringes, a valve, asuction generator, and a vacuum generator.
 14. A microfluidic flowdevice for separating a particle from a suspension flow into a secondfluid flow, the microfluidic flow device comprising: a microfluidicchannel comprising a first inlet port for receiving the suspension flow,a second inlet port for receiving the second fluid flow, a first outletport and a second outlet port, wherein said channel is adapted toreceive the suspension flow and the second fluid flow under laminarconditions; and an interface for translating the particle from thesuspension flow to the second fluid flow, wherein said first outlet portis adapted to receive at least a portion of the suspension flow exitingsaid channel and said second outlet port is adapted to receive theparticle in at least a portion of the second fluid flow exiting saidchannel.
 15. The microfluidic flow device of claim 14, wherein saidinterface comprises an optically transparent portion of said channel.16. The microfluidic flow device of claim 14, wherein said interfacecomprises two or more electrodes to provide an electric field in thecentral channel.
 17. The microfluidic flow device of claim 16, whereinsaid interface further comprises an electrical interconnect forreceiving electrical energy from the system and providing the electricalenergy to said two or more electrodes.
 18. The microfluidic flow deviceof claim 14, wherein said interface further comprises a magnet forproviding a magnetic field extending into said channel.
 19. Themicrofluidic flow device of claim 14, wherein said channel is adaptedsuch that an electric field may extend into said channel for translatingthe particle within the suspension flow.
 20. The microfluidic flowdevice of claim 19, wherein said field comprises at least one or more ofan optical trap, an electrical field and a magnetic field.
 21. Themicrofluidic flow device of claim 14, where in said interface comprisesa channel geometry for sorting the particle within the channel.
 22. Themicrofluidic flow device of claim 14, wherein said laminar conditionscomprise a Reynolds number of less than about
 1000. 23. The microfluidicflow device of claim 14, further comprising a third inlet port.
 24. Themicrofluidic flow device of claim 23, wherein said second and thirdinlet ports are adapted for providing a modulated flow rate.
 25. Themicrofluidic flow device of claim 14, wherein said channel is adapted toreceive the suspension flow and the second fluid flow in parallel flowsin the same direction.
 26. The microfluidic flow device of claim 14,wherein said channel is adapted to receive the suspension flow and thesecond fluid flow in parallel flows in the opposite direction.
 27. Themicrofluidic flow device of claim 14, wherein said channel comprises acartridge.
 28. The microfluidic flow device of claim 27, wherein saidchannel comprises a disposable cartridge.
 29. The microfluidic flowdevice of claim 14 further comprising a pressure differential generatorfor providing fluid flow in said channel.
 30. The microfluidic flowdevice of claim 29, wherein said pressure differential generatorcomprises one or more of the group comprising: a pump, a capillary forcegenerator, a gravity feed generator, an electro-osmosis system, asyringes, a valve, a suction generator, and a vacuum generator.
 31. Themicrofluidic flow device of claim 14, further comprising a third inletport for receiving a third fluid flow.
 32. The microfluidic flow deviceof claim 31, wherein said second inlet port enters said channel at afirst angle to said first inlet port and said third inlet port enterssaid channel at a second angle to said first inlet port.
 33. Themicrofluidic flow device of claim 32, wherein said second inlet port andsaid third inlet port provide a means for orienting the suspension flowin the channel.
 34. The microfluidic flow device of claim 33, whereinsaid means for orienting the suspension flow is adapted to orient thesuspension flow linearly.
 35. The microfluidic flow device of claim 33,where in said means for orienting the suspension flow is adapted tomodulate the position of the suspension flow within said channel.
 36. Amethod of separating a particle within a suspension comprising:receiving a suspension flow in a microfluidic channel, the suspensionflowing under laminar conditions; translating a particle within thesuspension flow; exiting a first portion of the suspension flow througha first outlet port, and exiting the particle along with a secondportion of the suspension flow through a second outlet port.
 37. Themethod of claim 36, wherein the translating of the particle includes theapplication of a field.
 38. The method of claim 37, wherein thetranslating of the particle includes the application of one or more ofthe group comprising: an electric field, an optical field and a magneticfield.
 39. The method of claim 36, wherein the translating of theparticle comprises using a channel geometry for sorting the particlewithin the channel.
 40. The method of claim 36, wherein the laminarconditions comprise a Reynolds number of less than about
 1000. 41. Themethod of claim 36 further providing a pressure differential forproviding fluid flow in the channel.
 42. The method of claim 41, whereinthe pressure differential is provided by one or more of the groupcomprising: a pump, a capillary force generator, a gravity feedgenerator, an electro-osmosis system, a syringes, a valve, a suctiongenerator, and a vacuum generator.
 43. A method of separating a particlefrom a suspension flow comprising: receiving a suspension flow in amicrofluidic channel, the suspension flowing under laminar conditions;receiving a second fluid flow in the channel, the suspension and thesecond fluid flowing under laminar conditions in the channel; separatinga particle from the suspension flow into the second fluid flow; exitingat least a portion of the suspension flow through a first outlet port;and exiting the particle in at least a portion of the second fluid flowthrough a second outlet port.
 44. The method of claim 43, wherein thetranslating of the particle includes the application of a field.
 45. Themethod of claim 44, wherein the translating of the particle includes theapplication of one or more of the group comprising: an electric field,an optical field and a magnetic field.
 46. The method of claim 43,wherein the translating of the particle comprises using a channelgeometry for sorting the particle within the channel.
 47. The method ofclaim 43, wherein the laminar conditions comprise a Reynolds number ofless than about
 1000. 48. The method of claim 43 further providing apressure differential for providing fluid flow in the channel.
 49. Themethod of claim 48, wherein the pressure differential is provided by oneor more of the group comprising: a pump, a capillary force generator, agravity feed generator, an electro-osmosis system, a syringes, a valve,a suction generator, and a vacuum generator.
 50. A cartridge for use insystem to separate a particle from a suspension flow, the cartridgecomprising: a microfluidic channel comprising an inlet port forreceiving a suspension flow under laminar conditions, a first outletport and a second outlet port; and an interconnect for connecting thecartridge to the system, wherein said microfluidic channel is adapted toreceive the suspension flow and provide an environment for translatingthe particle within the suspension flow, said first outlet port isadapted to receive a first portion of the suspension flow, and saidsecond outlet port is adapted to receive the particle in a secondportion of the suspension flow.
 51. The cartridge of claim 50 furthercomprising an interface for translating the particle within saidchannel.
 52. The cartridge of claim 51, wherein said interface comprisesan optically transparent portion.
 53. The cartridge of claim 51, whereinsaid interface comprises two or more electrodes to provide an electricfield in the central channel.
 54. The cartridge of claim 51, whereinsaid interface further comprises an electrical interconnect forreceiving electrical energy from the system and providing the electricalenergy to said two or more electrodes.
 55. The cartridge of claim 51,wherein said interface further comprises an magnet for providing amagnetic field extending into said channel.
 56. The cartridge of claim50, wherein said channel is adapted such that a field may extend intosaid channel for translating the particle within the suspension flow.57. The cartridge of claim 56, wherein said field comprises at least oneor more of an optical trap, an electrical field and a magnetic field.58. A microfluidic flow separator comprising: a channel means forreceiving a suspension flow under laminar conditions; a translatingmeans for translating a particle within the suspension flow; and a firstoutput means for exiting a first portion of the suspension flow; and asecond output means for exiting the particle in a second portion of thesuspension flow.
 59. A cartridge for use in system to separate aparticle from a suspension flow into a second fluid flow, the cartridgecomprising: a microfluidic channel comprising a first inlet port forreceiving the suspension flow, a second inlet port for receiving thesecond fluid flow, a first outlet port and a second outlet port, whereinsaid channel is adapted to receive the suspension flow and the secondfluid flow under laminar conditions, an interconnect for connecting thecartridge to the system, wherein said microfluidic channel is adapted toprovide an environment for translating the particle from the suspensionflow to the second fluid flow, said first outlet port is adapted toreceive at least a portion of the suspension flow, and said secondoutlet port is adapted to receive the particle in at least a portion ofthe second fluid flow.
 60. The cartridge of claim 59 further comprisingan interface for translating the particle within said channel.
 61. Thecartridge of claim 60, wherein said interface comprises an opticallytransparent portion.
 62. The cartridge of claim 60, wherein saidinterface comprises two or more electrodes to provide an electric fieldin the central channel.
 63. The cartridge of claim 60, wherein saidinterface further comprises an electrical interconnect for receivingelectrical energy from the system and providing the electrical energy tosaid two or more electrodes.
 64. The cartridge of claim 60, wherein saidinterface further comprises an magnet for providing a magnetic fieldextending into said channel.
 65. The cartridge of claim 59, wherein saidchannel is adapted such that a field may extend into said channel fortranslating the particle within the suspension flow.
 66. The cartridgeof claim 65, wherein said field comprises at least one or more of anoptical trap, an electrical field and a magnetic field.
 67. Amicrofluidic flow separator comprising: a channel means for receiving asuspension flow and a second fluid flow, the suspension flow and thesecond fluid flow under laminar conditions; a separator means forseparating a particle from the suspension flow into the second fluidflow; and a first output means for exiting at least a portion of thesuspension flow; and a second output means for exiting the particle inat least a portion of the second fluid flow.
 68. A microfluidic chemicaldispenser for dispensing a first fluid flow into a plurality ofreceptacles comprising: a first inlet port for receiving the first fluidflow; a second inlet port for receiving a second fluid flow at a firstangle to the first fluid flow; a third inlet port for receiving a thirdfluid flow at a second angle to the first fluid flow; a central channelfor receiving the first fluid flow, the second fluid flow and the thirdfluid flow under laminar conditions; a plurality of outlet ports forreceiving fluid flow from the central channel; a modulator means formodulating the relative flow rates of the second fluid stream and thethird stream to dispense the first fluid flow into said plurality ofoutlet ports.
 69. The microfluidic dispenser of claim 68, wherein thefirst fluid flow comprises a buffer fluid flow.
 70. The microfluidicdispenser of claim 68, wherein the first fluid flow comprises a solventfluid flow.
 71. A system for separating a particle from a solution in amicrofluidic flow device, the system comprising: a microfluidic channelcomprising an input port, a first output port and a second output port,said channel being adapted to receive the suspension via the input portunder laminar conditions; a detector for monitoring said channel andproviding an output; an information processor for receiving said outputand determining if the particle is present in said channel; and anactuator for translating the particle within said channel, wherein saidinformation processor triggers said actuator if the particle isdetected.